Tyrosination of [alpha]-tubulin controls the initiation of processive dynein-dynactin motility

• Published in: The EMBO journal Vol. 35; no. 11; p. 1175
• Main Authors: McKenney, Richard J, Huynh, Walter, Vale, Ronald D, Sirajuddin, Minhajuddin
• Format: Journal Article
• Language: English
• Published: Heidelberg Blackwell Publishing Ltd 01.06.2016
• Subjects: Cellular biology; Molecular biology; Motility; Proteins
• ISSN: 0261-4189; 1460-2075
• DOI: 10.15252/embj.201593071

Post-translational modifications (PTMs) of [alpha]/[beta]-tubulin are believed to regulate interactions with microtubule-binding proteins. A well-characterized PTM involves in the removal and re-ligation of the C-terminal tyrosine on [alpha]-tubulin, but the purpose of this tyrosination-detyrosination cycle remains elusive. Here, we examined the processive motility of mammalian dynein complexed with dynactin and BicD2 (DDB) on tyrosinated versus detyrosinated microtubules. Motility was decreased ~fourfold on detyrosinated microtubules, constituting the largest effect of a tubulin PTM on motor function observed to date. This preference is mediated by dynactin's microtubule-binding p150 subunit rather than dynein itself. Interestingly, on a bipartite microtubule consisting of tyrosinated and detyrosinated segments, DDB molecules that initiated movement on tyrosinated tubulin continued moving into the segment composed of detyrosinated tubulin. This result indicates that the [alpha]-tubulin tyrosine facilitates initial motor-tubulin encounters, but is not needed for subsequent motility. Our results reveal a strong effect of the C-terminal [alpha]-tubulin tyrosine on dynein-dynactin motility and suggest that the tubulin tyrosination cycle could modulate the initiation of dynein-driven motility in cells. Synopsis Post-translational modifications of tubulin can affect motor protein behavior on microtubules. This study reveals that microtubule tyrosination allows for robust initiation of mammalian dynein-dynactin processivity, but that tyrosination is dispensable once dynein is motile. Removal of alpha-tubulin carboxy-terminal tyrosine strongly decreases the interaction of the dynein-dynactin complex with microtubules. The dynein-dynactin complex has two separate microtubule binding domains. The CAP-Gly domain within the dynactin complex senses the tyrosination state of the microtubule and aids in the initiation of processive dynein motility. After the initiation of processive motility, the CAP-Gly interaction with the microtubule is not required for sustained dynein motility.